Impact of chromosome 17q deletion in the primary lesion of colorectal cancer on liver metastasis.

Colorectal cancer is a prevalent malignancy worldwide, and investigations are required to elucidate the underlying carcinogenic mechanisms. Amongst these mechanisms, de novo carcinogenesis and the adenoma to carcinoma sequence, are the most understood. Metastasis of colorectal cancer to the liver often results in fatality, therefore, it is important for any associated risk factors to be identified. Regarding the treatment of the disease, it is important to manage not only the primary colorectal tumor, but also the liver metastases. Previously, through gene variation analysis, chromosomal loss has been indicated to serve an important role in liver metastasis. Such analysis may aid in the prediction of liver metastasis risk, alongside individual responses to treatment, thus improving the management of colorectal cancer. In the present study, we aimed to clarify a cause of the liver metastasis of colorectal cancer using comparative genomic hybridization analysis. A total of 116 frozen samples were analyzed from patients with advanced colorectal cancer that underwent surgery from 2004 to 2011. The present study analyzed mutations within tumor suppressor genes non-metastatic gene 23 (NM23), deleted in colorectal carcinoma (DCC) and deleted in pancreatic carcinoma, locus 4 (DPC4), which are located on chromosomes 17 and 18 and have all been reported to affect liver metastasis of colorectal cancer. The association between chromosomal abnormalities (duplication and deletion) and liver metastasis of colorectal cancer was evaluated using comparative genomic hybridization. Cluster analysis indicated that the group of patients lacking the long arm of chromosome 17 demonstrated the highest rate of liver metastasis. No significant association was observed between the frequency of liver metastases for synchronous and heterochronous colorectal cancer cases and gene variation (P=0.206). However, when these liver metastasis cases were divided into the synchronous and heterochronous types, the ratio of each was significantly different between gene variation groups, classified by the existence of the 17q deletion (P=0.023). These results indicate that the deletion of 17q may act as a predictive marker of liver metastasis in postoperative states.

Proteomic analysis of rat brains in a model of neuropathic pain following exposure to electroconvulsive stimulation.

Some reports have shown that electroconvulsive shock therapy is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. This study analyzes changes in protein expression in the brainstems of neuropathic pain model rats with or without electroconvulsive stimulation (ECS). A neuropathic pain model rat is produced by chronic constrictive injury (CCI) of the sciatic nerve. An ECS was administered to rodents once daily for 6 days after the CCI operation. After ECS, the latency to withdrawal from thermal stimulation was significantly increased. The expression of several proteins was changed after CCI. Ten proteins that increased after CCI then had decreased expression levels (close to control) after ECS, and 8 proteins that decreased after CCI then had increased expression levels (close to control) after ECS. In conclusion, ECS improved thermal hypersensitivity in a rat CCI model. Proteomic analysis showed that altered expression levels of proteins in the brainstem of CCI model rats returned to close to control levels after ECS, including many proteins associated with pain. This trend suggests an association of ECS with improved hypersensitivity, and these results may help elucidate the mechanism of this effect.

Changes in neuropeptide Y gene expression in the spinal cord of chronic constrictive injury model rats after electroconvulsive stimulation.

Some reports have shown that electroconvulsive shock therapy (ECT) is effective for treating refractory neuropathic pain. However, its mechanism of action remains unknown. We have previously shown that electroconvulsive shock (ECS) improved thermal hypersensitivity in chronic constrictive injury (CCI) model rats and simultaneously elevated the neuropeptide Y (NPY) expression in the brain of these rats. In this study, we examined changes in the expression of NPY in the spinal cord of a CCI model. The rat model of CCI was established by ligating the left sciatic nerve. ECS was administered to the rats once daily for six days on days 7-12 after the operation using an electrical stimulator. RT-PCR was used to measure NPY mRNA expression in both the right and left L5 dorsal spinal cords on the 14th day after the operation. NPY gene expression was decreased in the dorsal spinal cords after ECS; however, no differences in NPY expression were observed between the right and left side of dorsal spinal cords, suggesting that the effect of changes in NPY expression after ECS on the improvement of neuropathic pain is not directly related to the spinal cord, but mainly to the upper central nerves.

A case of cancer pain management by long-term intrathecal PCA.

Titration of oral or intravenous medication is the preferred method of pain management for most patients with cancer pain. However, some patients experience insufficient pain relief or considerable adverse effects from systemic opioids. For these reasons, the control of severe cancer pain continues to present a variety of challenges to clinicians. We report our experience of successfully managing cancer pain in a patient by means of long-term intrathecal administration of morphine, bupivacaine, and racemic ketamine via a patient-controlled delivery system. This therapy reduced the patient's nausea, vomiting, and somnolence, led to early hospital discharge, and increased her level of daily activity. There were no signs of motor paralysis, psychomimetic alteration, neurological dysfunction, or infection related to the intrathecal route during treatment. Intrathecal therapy is an effective treatment in terminally ill patients.

Electroconvulsive stimulation (ECS) increases the expression of neuropeptide Y (NPY) in rat brains in a model of neuropathic pain: a quantitative real-time polymerase chain reaction (RT-PCR) study.

OBJECTIVES: Electroconvulsive shock therapy (ECT) has been widely used as an effective and established treatment for refractory depression and schizophrenia. Some reports have shown that ECT is also effective for treating refractory neuropathic pain. DESIGN: In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from day 2 after surgery. An electroconvulsive shock (ECS) was administered to rodents once daily for 6 days on days 7-12 after CCI operation using a pulse generator. Thermal and mechanical stimulation tests were performed to assess pain thresholds. Real-time polymerase chain reaction was used to measure the gene expression levels for 5HT(1A)R, 5HT(2A)R, neuropeptide Y (NPY), and GABAA(alpha1)R in the brain. RESULTS: After ECS, the latency to withdrawal from thermal stimulation was significantly increased; however, pain withdrawal thresholds in response to mechanical stimulation were not significantly changed. Expression ratios of NPY were significantly greater after ECS. CONCLUSION: Symptoms of neuropathic pain improved and expression of NPY in the brain was increased in CCI model rats after ECS, suggesting that changes in the expression of NPY in the brain may be related to the mechanism of action of ECT in treating neuropathic pain.

Clinical role and efficacy of landiolol in the intensive care unit.

Beta-adrenergic receptor blockers have proved to be effective for the management of various cardiovascular diseases and the prevention of perioperative cardiac events and cerebrovascular accidents. Landiolol is a short-acting beta-blocker, with high beta 1-selectivity and a short duration of action. We thought landiolol was valuable and suitable for intensive care unit (ICU) patients, and conducted a retrospective study. The records of 80 patients (58 post-surgical patients; group S and 22 internal medicine patients; group IM) were reviewed. Thirty-seven (64%) of the group S patients were post-coronary artery bypass graft surgery, and the IM group consisted mostly of patients with acute myocardial infarction. The most common indication for landiolol in group S was the prevention of myocardial ischemia (50%), and in group IM, it was atrial fibrillation (45%). The median infusion rate of landiolol was 5 microg.kg(-1).min(-1) and the median infusion time was 2 days. Twenty-six patients were continued on oral beta-adrenergic receptor blockers. Landiolol reduced heart rate significantly without reducing blood pressure, and stabilized hemodynamics. We confirmed that landiolol is valuable as a bridge to starting oral beta-adrenergic receptor blockers and as an anti-arrhythmic agent, and that it is suitable for ICU patients due to its high beta 1-selectivity and rapid onset and offset of action.

The prolonged analgesic effect of epidural ropivacaine in a rat model of neuropathic pain.

BACKGROUND: In clinical practice, the analgesic effects of epidurally administered local anesthetics on chronic pain sometimes outlast the duration of drug action expected from their pharmacokinetics. To investigate the underlying mechanisms of this prolonged effect, we examined the effects of ropivacaine, a local anesthetic, on pain-related behavior in a rat model of neuropathic pain. We also analyzed changes in the expression of nerve growth factor (NGF), which is involved in plasticity of the nociceptive circuit after nerve injury. METHODS: In a rat model of neuropathic pain produced by chronic constrictive injury (CCI) of the sciatic nerve, thermal hyperalgesia, and mechanical allodynia were observed from Day 3 after surgery. Ropivacaine or saline was administered through an epidural catheter once a day, every day, and from Days 7-13 after the CCI operation. NGF content was measured in the L4 dorsal root ganglion, the hindpaw skin, the L4/5 dorsal spinal cord, and the sciatic nerve, using enzyme immunoassay. RESULTS: The latency to withdrawal from thermal stimuli on the ipsilateral paw pads of CCI rats was significantly increased 4 days after the beginning of ropivacaine treatment, and thermal hyperalgesia was almost fully relieved. Similarly, mechanical allodynia was partially reduced after ropivacaine treatment. NGF content was increased in the L4 dorsal root ganglion on the ipsilateral, but not the contralateral, side, in CCI rats treated with ropivacaine. CONCLUSION: Repetitive administration of ropivacaine into the epidural space in CCI rats exerts an analgesic effect, possibly by inducing a plastic change in the nociceptive circuit.

Incessant non-sustained ventricular tachycardia after stimulus of electroconvulsive therapy with atropine premedication?

Electroconvulsive therapy (ECT) is an effective and safe treatment for a variety of neuropsychiatric disorders. Premedication with atropine has been recommended in order to avoid bradycardia and transient asystole induced by ECT. In contrast, some other arrhythmias can happen such as atrial flutter and fibrillation. But ventricular tachycardia is rare. Reported herein is a case of incessant non-sustained ventricular tachycardia, possibly triggered by atropine premedication.

[Low oxygen saturation during early postoperative period in adult patients receiving opioids by intravenous patient-controlled analgesia].

BACKGROUND: Patient-controlled analgesia (PCA) provides effective postoperative analgesia. However, there are few reports concerning the adverse outcome of respiratory depression. METHODS: We measured arterial oxygen saturation (SpO2) continuously during early postoperative period in 38 adult patients receiving opioids by intravenous PCA. We assessed the severity and incidence of desaturation, defined as SpO2 below 90% for more than 10 seconds. RESULTS: Nine patients showed desaturation and were studied after the surgery of the extremities, body surfaces, thorax or abdomen. Two patients showed desaturation with combination of surgery of long duration and obesity. Six patients, all of whom with liver cirrhosis, underwent thoracic and abdominal procedures, and showed desaturation because of respiratory dysfunction and hypoxemia caused by the surgery itself. One patient showed respiratory depression due to the opioids. CONCLUSIONS: We conclude that careful monitoring with a pulse oximeter and giving oxygen are essential to prevent desaturation during early postoperative period.